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Biomedical subjects

L E Lins

Publications and source records attributed to L E Lins.

At least 19 recordsLinked to original sources

Long-term prognosis of post-infectious renal scarring in relation to radiological findings in childhood--a 27-year follow-up.

In a previous report the long-term prognosis of 30 patients with renal scarring after pyelonephritis in childhood was described. In this study, we have related the extent of renal scarring present in childhood to the conditions in early adulthood. A radiological progression of scarring from childhood to adulthood was seen in one-third of the kidneys. The 7 patients with bilateral scarring in childhood had a smaller renal area, lower glomerular filtration rate and higher plasma vasopressin at follow-up than 13 healthy controls. The 20 patients who had unilateral scarring in childhood had a smaller renal area, lower glomerular filtration rate, higher diastolic blood pressure and higher plasma renin at follow-up than controls; 4 had hypertension. The most important finding was that children with unilateral disease are at risk of serious long-term complications. Filtration fraction at follow-up was higher in patients with extensive renal scarring in childhood compared with those with a normal renal area or small scars in childhood (r = -0.43, P less than 0.05). This may indicate glomerular hyperfiltration by remnant glomeruli. This paper emphasizes t the potential seriousness of childhood urinary tract infections especially when early infantile infections are overlooked. A follow-up of more than 4 decades may be necessary before the ultimate prognosis can be established, especially in patients with unilateral renal disease. It is advised that most patients with post-infectious renal scars are followed as high-risk patients, and that treatment continuity is established between paediatricians, nephrologists and, when required, obstetricians.

Adolescent

Binding of dietary cobalt to sarcoplasmic reticulum proteins.

It has previously been shown that cobalt accumulates in the myocardium of rats, mainly the sarcoplasmic reticulum (SR) and the mitochondrial inner membrane. In order to investigate the mode of accumulation of cobalt in the SR, rats were given a dietary cobalt supplementation of 40 mg of CoSO4 x 7H2O kg-1 body wt, after which the rats were sacrificed and the sarcoplasmic reticulum was isolated. The SR proteins were subjected to analysis by polyacrylamide gel electrophoresis followed by protein staining and determination of the content of cobalt in each protein band. The major cobalt-binding protein was found to have a molecular weight of about 100,000; a 200,000 molecular weight protein was also found to bind cobalt, although less extensively. These results suggest that cobalt is bound to the monomeric and dimeric forms of Ca(2+)-ATPase in the SR of the myocardium.

Animals

Effective anticoagulation by a low molecular weight heparin (Fragmin) in hemodialysis with a highly permeable polysulfone membrane.

The efficacy and kinetics of a low molecular weight heparin fragment (LMWH-fragment, Fragmin) were studied during one hemodialysis session with a highly permeable polysulfone membrane and compared to a second dialysis session using a conventional cuprophane membrane. All patients received 5000 U of Fragmin given as an injection into the arterial line at start of dialysis. The anticoagulative efficacy was evaluated by measuring plasma fibrinopeptide A concentrations. LMWH-fragment concentrations in plasma and ultrafiltrate were determined by an amidolytic activity assay and by a radioimmunoassay using a monoclonal antibody. During hemodialysis with cuprophane and polysulfone membranes the fibrinopeptide A concentrations were low indicating adequate anticoagulation. LMWH concentrations in plasma did not differ in the two membranes at any time. The LMWH-fragment in the ultrafiltrate could neither be detected with the amidolytic assay nor with the radioimmunoassay. We conclude that a single injection of Fragmin effectively prevents clotting during hemodialysis with a highly polysulfone membrane. No significant amounts of the anticoagulant are lost over the dialysis membrane.

Aged

Blood pressure reduction during hemodialysis correlates to intradialytic changes in plasma volume.

Blood pressure alterations during hemodialysis were related to changes in body fluid in 14 patients with chronic renal failure. Changes in plasma volume (PV) and extracellular volume (ECV) were calculated from determinations of fluid volumes before and after hemodialysis, using 125I-albumin and 51Cr EDTA respectively. Reduction in body water was estimated from body weight changes. Weight loss was 3.3 +/- 0.3 kg (range 1.8-6.0 kg). The relative reduction of fluid was greater in the ECV, 21.6 +/- 3.2%, compared to plasma volume, 6.9 +/- 1.8%. The reduction in systolic blood pressure was related to both absolute (r = 0.66, p less than 0.05) and relative PV reduction (r = 0.72, p less than 0.02). There was no correlation between blood pressure reduction and weight loss or ECV changes. Only minor alterations were found in diastolic blood pressure. Plasma volume maintenance relates to blood pressure changes. Plasma volume monitoring could be useful for improving intradialytic hemodynamic control.

Adult

Effects of exercise training in predialytic uremic patients.

We examined the effects of physical training in 10 predialytic uremic patients (7 men, 3 women, mean age 47 +/- 8 years) with an average glomerular filtration (GFR) of 15 +/- 7 ml/min x 1.73 m2. All 10 patients participated in an exercise programme 3 times/week for 3 months and were compared to a control group of 9 patients with comparable baseline variables. The exercise group increased its maximal exercise capacity measured by standardized exercise test on a bicycle ergometer, from an average 159 +/- 49 to 174 +/- 57 W (p less than 0.01). They also showed a decrease in heart rate at equal load (138 +/- 29-123 +/- 18 beats/min, p less than 0.05). The control group did not change its exercise capacity (171 +/- 60 and 171 +/- 65 W, respectively, NS), nor its heart rate at equal load (124 +/- 24 and 123 +/- 24 beats/min, respectively, NS). Thigh muscular function assessed by static endurance increased from a median 77 s (range 27-197) to 113 s (range 66-201), p less than 0.002. Dynamic muscular endurance increased from a median number of 41 movements (range 28-105) to 93 movements (range 45-139), p less than 0.001. The corresponding figures for the controls were: static endurance 60 (range 20-209) and 47 s (range 9-203), respectively, NS; dynamic endurance 53 (range 19-190) and 43 movements (range 10-126), respectively, NS. Total hemoglobin, blood volume, GFR, blood pressure and echocardiographic variables remained unchanged during the observation period. We conclude that in predialytic uremic patients, physical training improves exercise capacity mainly due to an improved muscular function.

Adult

Whole body impedance measurements reflect total body water changes. A study in hemodialysis patients.

Fluid volume changes during hemodialysis was monitored by continuous whole body impedance measurements. The fluid changes recorded using this method was compared to fluid volume changes measured in plasma water (PV) using 125I-albumin, and extracellular volume (ECV) using 51Cr-EDTA before and after treatment, and total body water (TBW) changes reflected by continuous bed scale monitoring. Changes in impedance correlated to TBW changes, r = 0.80, p less than 0.001, while correlations to changes in ECV and PV were: r = 0.57 and r = 0.55, respectively, p less than 0.05. Alterations in body fluid volumes recorded with whole body impedance is best correlated to total body water changes. The use of continuous whole body impedance monitoring has been shown to offer a simple non-invasive method for recording total body water changes during hemodialysis.

Aged

The effect of cobalt on mitochondrial ATP-production in the rat myocardium and skeletal muscle.

Cobalt has been shown to accumulate in the myocardium of uraemic patients and has been suggested as a myocardial toxin inhibiting mitochondrial respiration. In order to study the cellular effects of cobalt exposure three groups of rats (n = 12 per group) were fed a diet containing 12% protein without supplementation or with 20 mg and 40 mg CoSO4 7 H2O/kg body weight/day respectively. After 8 weeks the hearts and soleus muscles were removed. Cobalt in tissues and in four cell fractions were analysed with neutron-activation analysis (ng/g wet weight and ng/mg protein respectively). Mitochondrial respiration was analysed as ATP-production rate using pyruvate + malate and palmitoyl-carnitine + malate as substrate. The ATP-production from pyruvate + malate was unchanged in both heart and skeletal muscle in the exposed animals. With palmitate as substrate, the heart muscle showed a slightly lower ATP-production rate (p less than 0.05) after the 20 mg cobalt dose, but the rate was unchanged in the group with higher cobalt intake. No changes in ATP-production rate from palmitate was observed in soleus muscle. The microsomal (100,000 g) fraction in the myocardial cells contained significantly higher cobalt concentrations compared to the mitochondrial fraction in both the unexposed (1.4 ng/mg protein vs 0.19, p less than 0.05) and exposed rats (53.4 ng/mg protein vs 13.2, p less than 0.005). In conclusion, cobalt showed a large accumulation in myocardial cells, without significant effects on mitochondrial ATP-formation rate from oxidation of pyruvate or palmitate and with the highest cobalt content contained in the microsomal (100,000 g) fraction.

Adenosine Triphosphate

The intracellular distribution of cobalt in exposed and unexposed rat myocardium.

The intracellular distribution of cobalt was analysed in the myocardium of exposed and unexposed rats. The exposed rats were given a dietary cobalt supplementation of 40 mg CoSO4.7 H2O/kg body weight for 8 weeks. The mitochondrial fraction showed the greatest relative increase in cobalt: 0.09 ng/mg protein in the unexposed rats to 8.43 ng/mg protein in the exposed rats. In the exposed rats the submitochondrial particles had the highest levels of cobalt: 19.43 ng/mg protein, followed by the sarcoplasmatic reticulum: 12.3 ng/mg protein. The microsomal 44,000 g supernatant also showed an increase, although the levels remained low (0.51 ng/mg protein in the exposed animals). Apparently the calcium-storing organelles had the highest levels of cobalt. This could affect calcium flux in myocardial cells and, secondarily, tension development in cardiac muscle.

Animals

Altered vasopressin release and osmotic regulation during exercise in patients with pyelonephritic renal scarring.

Children and adults with pyelonephritic renal scarring are at high risk of developing hypertension. The objectives of the present investigation were to study if it is possible to detect early disturbances in blood pressure (BP) control and secretion of hormones involved in the regulation of BP and renal function, in patients with renal scarring. We studied renal function at rest, BP regulating hormones and BP at rest and during graded bicycle exercise until exhaustion. The 22 patients with renal scarring had significantly lower glomerular filtration rate and renal blood flow than the 13 healthy age-matched controls. At rest, the patients had higher diastolic (p less than 0.01) and mean arterial BP (p less than 0.02), higher plasma renin (p = 0.06) and higher serum osmolality (p less than 0.001) but there were no significant differences in systolic BP, angiotensin II, aldosterone or vasopressin (AVP). The patients with renal scarring had higher AVP than the controls during light and moderate exercise and 15 min after maximal exercise. BP and renal hormones increased significantly but similarly during exercise in both patients and controls. There were no significant differences in BP control or release of pressure-regulating hormones at maximal exercise. Maximal exercise did not evoke pathological BP response in normotensive young adults with pyelonephritic renal scarring. The increase in serum osmolality and hypersecretion of AVP during light and moderate exercise may be important in the pathogenesis of hypertension in this group of patients.

Adult

Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up.

OBJECTIVE: Determination of the long term incidence of uraemia, hypertension, and toxaemia in pregnancy associated with non-obstructive focal renal scarring after pyelonephritis in childhood 25-35 years earlier. DESIGN: 27 Year follow up of patients with non-obstructive focal scarring identified from a retrospective review of intravenous urograms performed in childhood between 1951 and 1967. SETTING: Paediatric primary referral centre and urological clinic in tertiary referral centre. PATIENTS: 30 Patients (mean age 33 (range 22-41] with non-obstructive focal renal scarring first detected between 1951 and 1967 and a history of febrile urinary tract infection. MAIN OUTCOME MEASURE: Hypertension and complications of renal damage. RESULTS: Three patients had developed end stage renal disease, seven had developed hypertension, two of 16 women had a history of toxaemia during pregnancy, and seven patients had undergone renal surgery during follow up. Of the 20 patients who had neither had renal surgery nor had end stage renal disease, all had a significantly lower glomerular filtration rate and renal plasma flow and higher diastolic blood pressure, mean arterial blood pressure, plasma renin activity, and serum beta 2 microglobulin concentration than 13 healthy age matched controls. Diastolic blood pressure and plasma renin activity were positively correlated (r = 0.50, p less than 0.05) and so were fractional sodium excretion and both systolic and diastolic blood pressures (r = 0.54, p less than 0.01, r = 0.51, p less than 0.01 respectively). The progress of renal damage was unrelated to the incidence of recurrent infections. CONCLUSIONS: Children with focal renal scarring due to pyelonephritis are at high risk of serious long term consequences. It is essential that they are given adequate attention and care during adolescence and pregnancy.

Adult

Experimental and immunohistochemical studies on the possible role of parathyroid hormone in uraemic pruritus.

Secondary hyperparathyroidism has been suggested as a cause of itching in chronic renal failure. The aim of the present study was to evaluate the possible role of parathyroid hormone (PTH) in pruritus affecting patients undergoing maintenance haemodialysis. In agreement with our previous findings, patients with pruritus had significantly (P less than 0.01) higher serum levels of PTH fragment 53-68 (m-PTH53-68) than patients without pruritus, 47.7 +/- 40.0 and 23.4 +/- 17.1 micrograms l-1 respectively. Serum concentrations of other substances including calcium, phosphate and magnesium did not differ between the two groups of patients. Intradermal injections of human PTH1-34 and PTH44-68 failed to evoke any acute or delayed cutaneous reactions in either patients or controls. Immunohistochemical investigations of skin biopsies from uraemic patients using several different antibodies against PTH were negative. Thus, the present results do not support PTH as a peripheral mediator of uraemic itching.

Adult

Factors influencing physical working capacity in renal transplant patients.

Clyne N, Jogestrand T, Lins L-E & Pehrsson SK. Division of Nephrology and Cardiology, Department of Medicine and Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden. We have examined uraemic patients' exercise capacity, and the factors influencing this capacity, before and after successful renal transplantation. Eleven uraemic patients (mean age 41 +/- 10 years) with an average glomerular filtration rate (GFR) of 5 +/- 4 ml/min x 1.73 before and 45 +/- 19 ml/min x 1.73 after transplantation participated in the study. The maximal exercise capacity, measured by standardized exercise test on a bicycle ergometer, averaged 106 +/- 25 W before and 126 +/- 35 W (p less than 0.05) after transplantation. The patients interrupted the tests prior to and after transplantation because of general fatigue, leg tiredness or both. No patient experienced angina pectoris. All, but one, had a normal ECG reaction during exercise. Total haemoglobin (THb) was 55 +/- 8% of the expected normal before and 84 +/- 19% after transplantation (p less than 0.01). The increase in working capacity was linearly correlated to the increase in THb (r = 0.84, p less than 0.01), but not to the improvement in GFR nor to the decrease in parathyroid hormone. In conclusion, successful renal transplantation improves working capacity. The results indicate that an increased THb is a major determinant for this increase in working capacity.

Adult

The sensitivity of uremic and normal human skin to histamine.

Cutaneous reactions induced by intradermal histamine injection were studied in uremic patients with and without pruritus who were undergoing maintenance hemodialysis and also in healthy subjects. Flare reactions were significantly smaller in both groups of patients than in controls. However, the itch responses following histamine injection were greater in patients with pruritus than in non-pruritic patients and healthy subjects, indicating an augmented sensitivity to pruritogens in these patients. The development of histamine tachyphylaxis was demonstrated in healthy human skin. After repeated histamine injections at intervals of 90 min, both itch and flare responses decreased rapidly. A similar decline in histamine reactivity occurred when the interval between injections was extended to 24 h. The phenomenon of histamine tolerance was confirmed in 2 uremic patients.

Adult

Vasospastic phenomena in patients treated with beta-adrenoceptor blocking agents.

Twenty-one patients developed Raynaud's phenomenon during treatment with beta-adrenoceptor blocking agents. The vasospastic symptoms were obviously related to the treatment, but their pathogenesis is still controversial. A decrease in cardiac output might explain the phenomenon. According to our very preliminary data an alpha-adrenergic dominance caused by a direct effect on the peripheral circulation seems more probable. Vasospastic symptoms may arise after treatment with both cardioselective and non-selective beta blocking agents. Cautious prescription of beta blocking drugs to patients with preexisting peripheral vascular disease is recommended.

Adrenergic beta-Antagonists

Renal function in hypercalcemic dogs during hydropenia and during saline infusion.

The effects of calcium-gluconate infusions on renal function were studied in unanesthetised dogs. Each dog was studied during hydropenia and saline infusion. Hypercalcemia, mean serum calcium 3.85 mmol/l (hydropenia) and 3.62 mmol/l (saline infusion), increased fractional excretion of sodium (CNa/CIn), calcium (CCa/CIn), and magnesium (CMg/CIn). The increase was significantly higher in saline-expanded dogs than in hydropenic dogs. Fractional excretion of potassium (CK/CIn) was increased in hydropenia but remained unchanged in saline-expanded animals. Fractional excretion of phosphate (Cp/CIn) was not consistently changed by hypercalcemia. Fractional excretion of chloride (CCl/CIn) was markedly increased in saline-expanded dogs but was not changed in hydropenia. Urine osmolality was reduced in hydropenic dogs but unchanged in saline-expanded dogs. In hydropenic as well as in saline-expanded dogs tubular reabsorption of solute-free water (TcH2O/CIn) increased during the first hour of hypercalcemia. In hydropenic dogs hypercalcemia caused a slight but significant decrease in blood pH, standard bicarbonate, and base excess. In hydropenic as well as in saline-expanded dogs glomerular filtration rate (CIn), renal plasma flow (CPAH), and filtration fraction were unaffected.

Acid-Base Equilibrium